Development of a Hybrid Artificial Liver Support System Using Puf/Spheroid Packed-Bed

Abstract

Spherical multicellular aggregates of adult rat hepatocytes (spheroid) which have tissue like structure, were formed and immobilized in the pores of polyurethane foam (PUF) which was used as a culture substratum. These hepatocyte/spheroids, about 100 µm in diameter, have maintained higher differentiated functions (the albumin secretion activity and the urea synthesis activity) than those of hepatocyte/monolayer for about 3 weeks. Then, we designed a prototype module of an artificial liver support system using a PUF/spheroid packed-bed, in which hepatocyte/spheroids were immobilized at high density (0.5~1.0x107 cells/cm3-PUF). We also developed the rat extracorporeal circulation system and examined the performance of hybrid artificial liver in an ex vivo extracorporeal experiment with a D-galactosamine induced acute hepatic failure rat. The blood ammonia concentration, which was one of the toxic causal substances for hepatic coma, decreased at normal level after the extracorporeal circulation for 3 hours and the hepatic failure rat was recovered by this hybrid artificial liver.